Graduation Year

2018

Document Type

Dissertation

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Degree Granting Department

Chemistry

Major Professor

Arjan van der Vaart, Ph.D.

Committee Member

Ioannis Gelis, Ph.D.

Committee Member

Brian Space, Ph.D.

Committee Member

Randy Larsen, Ph.D.

Committee Member

Stephen Liggett, Ph.D.

Keywords

Biomolecules, Simulation, Spider Silk, Computational Chemistry

Abstract

Biomolecule structural fluctuations determine function, regulating numerous biological processes My research has shed light on several interesting cases in which structural fluctuations have been identified to assess functional differences. Chapter 2 discusses the effects of structural rearrangement of the β2-β3 loop on the DNA binding affinity of the type 6 human papillomavirus E2 protein. Chapter 3 investigates the effects of phosphorylation on the C-terminal domain of Cdc37, a protein important in the Hsp90 chaperone cycle. Chapter 4 studies the effects on cyclycization on the conformational fluctuations of a γ-AApeptide used for high-throughput libraries. Chapter 5 is a structural study on a mini-fibril of spider dragline silk, in which a native-like ensemble was generated using temperature replica exchange. Chapter 6 investigates the structural features of repetitive motifs found in spider dragline silk when subject to both dope-like and fiber-like conditions. Chapter 7 elucidates conformational differences between the RXRα and the RXRβ ligand-binding domains and seeks to understand the atomic basis for different ligand binding affinities. This body of work has contributed to the understanding of conformational fluctuations and changes that occur in protein-DNA binding systems, drug-binding, regulation of chaperones via post-translations modifications and spider dragline silk.

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